1. Field of the Invention
The present invention relates to a cell regulator, especially relates to a mitochondria regulator.
2. The Prior Arts
No matter at rest or at work, normal function of human organs and tissues must have adenosine triphosphate (abbreviated as ATP) involved. In cells about 90% of the ATP is generated by mitochondria, and oxygen is consumed when mitochondria produces ATP. It is estimated that 90% of the oxygen in the cell are used by mitochondria. Furthermore, when mitochondria metabolize three major nutrients (fatty acids, carbohydrates, and amino acids) efficiently, oxygen will be consumed no matter energy generated or heat generated. Therefore, mitochondria itself is high oxygen consuming organelle and mitochondria is the site with highest frequency of oxidation and reduction reactions in the cell.
In human cell, skeletal muscle use ATP most frequently. ATP required for muscle fiber contraction is dependent on vigorous oxidative phosphorylation reaction in mitochondria. Therefore, there are more blood vessels around the muscle fibers in order to provide enough oxygen and fuel molecules (i.e., fatty acids, carbohydrates, or amino acids).
In addition, fatty tissues in the body can be classified into two groups, namely white adipose tissue and brown adipose tissue, according to their mitochondria type, distribution site in the body and color. The white adipose tissue has smaller and less amount of mitochondria, and the fatty acids in the tissue serve as energy source during rest state and oxidative exercise. On the other hand, the brown adipose tissues are mainly distributed in the shoulder, neck and arm of hibernating animals, and have abundant of mitochondria. Because mitochondria contain many cell pigments, these pigments makes brown adipose tissue exhibits brown color.
Although oxidative metabolism in cellular mitochondria produces ATP, mitochondria in the brown adipose tissue are not designed to produce ATP as a mode of energy output. Especially, there are many thermogenin distributed on the inner membrane of mitochondria in the brown adipose tissue. The thermogenin is a protein that consumes all energy generated by oxidation of fuel molecules, thus no ATP can be generated. Instead, heat is produced and the energy is dissipated. Because the mitochondria in the brown adipose tissue are large and abundant, more heat is produced.
Therefore, brown adipose tissues rely on the unique heat generation system of mitochondria to oxidize fatty acids at low temperature or during ingestion. Without exercise, hibernating animals and newborn babies can also generate heat to adapt cold environment. Because the central temperature regulation system in the newborn babies is not mature, the heat production mode of brown adipose tissue is especially important to protect the newborn babies from tremble reaction. The thermogenin in the mitochondria of brown adipose tissue is an important factor to keep thermostasis.
The above thermogenin apply uncoupling reaction to reduce ATP generation in mitochondria, increase basic metabolism consumption and dissipate energy in heat form. Uncoupling protein (abbreviated as UCP) plays an important role as regulator in mitochondrial's uncoupling reaction. UCPs are proteins located in the inner membrane of mitochondria and there are three main expression forms, including UCP1, UCP2, and UCP3. UCP2 and UCP3 are mainly responsible for regulation of reactive oxygen species (ROS) synthesis. The expression levels of UCP2 and UCP3 are far less than that of UCP1 in mammals. UCP1, also called as “thermogenin”, is mainly expressed in brown adipose tissue and is mainly responsible for adaptive regulation of heat generation and heat consumption.
Peroxisome proliferator-activated receptor γ coactivator-1 (PGC1α), tfam (mitochondrial transcription factor A) and NrF1 (nuclear respiratory factor 1) are important transcription regulation factors in mitochondria biosynthesis, wherein PGC1α is a coactivator of PPARγ that mainly distributed in high oxygen consumption tissue, such as heart tissues or brown adipose tissues. PGC1α can regulate mitochondria biosynthesis and energy metabolism. Furthermore, tfam can bind to mitochondria DNA to regulate mitochondria transcription and replication, and NrF1 is also involved in regulation of mitochondria gene transcription. Prior studies have shown that increase of PGC1α□ concentration in the muscle can stimulate expression of abovementioned NrF and tfam of mitochondria genes, decrease possibility of obesity owing to aging, and decrease possibility of diabetes, and prolong life.
The material, bitter gourd, is a common traditional Chinese medicine. However, to the best of our knowledge, the bitter gourd has never been reported in regulation the mitochondria. The mitochondria regulator can modulate mitochondrial related proteins and genes effectively to enhance heat and energy generation efficiency. The mitochondria regulator composition of the present invention can be used as a healthy food composition or pharmaceutical composition for treatment of disease due to deficiency of thermogenin or mitochondria, mitochondrial dysfunction, mitochondria malfunction, or mitochondria dysregulation.